An upgrade of an existing 600 MHz NMR spectrometer used primarily for structural biology applications is proposed. The upgrade will replace a 17 year old Varian INOVA console with a new Bruker Avance III HD 600 High Performance Digital NMR Console and an existing cryobay with a Bruker cryoplatform. The upgrade will allow the use of a high sensitivity cryoprobe that is optimized for 13C (and 15N) detection along with 1H and 2H decoupling. The instrument is being placed in a well-staffed and supported NMR facility that serves the University of Georgia (UGA) scientific community, as well as a number of additional scientists throughout the region. The ability to observe 13C directly with high sensitivity will add to the facility a capability that is unique, and one that is becomin increasingly important in the characterization of biomolecular systems. These systems include large proteins or proteins that are parts of large complexes, proteins with intrinsically disordere regions, and natural products (including some glycans) that have significant numbers of non- protonated carbon sites. In addition to this unique capability, the system will execute, with sensitivity comparable or greater than non-cryo systems, the traditional proton detected triple resonance experiments that have become so important to structure determination of biomedically important proteins. In the latter case the more reliable and up-to-date system will add important capacity to serve the growing number of NMR users who pursue NMR-based structural work at UGA. Seven major users and three minor users have provided research descriptions as a part of this proposal. Their projects impact on areas such as: the role of glycans in development and metastasis, protein modifications in response to environmental stress, protein interactions in cell signaling and immune response, regulation of virulence factors in pathogenic bacteria, and improving drug efficacy through regulation of transport and metabolism. Seven of the ten users are currently supported by NIH grants, and we expect additional NIH support as the newly added faculty establish their UGA research programs. The requested instrumentation will allow them that access to NMR instrumentation needed for their current research, and it will allow them to adopt new experimental protocols that allow them to attack ever more complex problems in the future.